Complosome — the intracellular complement system

Nature Reviews Nephrology, Год журнала: 2023, Номер 19(7), С. 426 - 439

Опубликована: Апрель 13, 2023

Язык: Английский

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Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16515 - 16515

Опубликована: Ноя. 20, 2023

The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect organism against infections support repair damaged tissues. Alterations in this complex machinery play a role pathogenesis different diseases. Core proteins C3 C5, their activation fragments, receptors, regulators have been shown be active intracellularly as complosome. kidney is particularly vulnerable complement-induced damage, emerging findings revealed system dysregulation wide range disorders, including glomerulopathies ischemia-reperfusion injury during transplantation. Different studies that important component tumorigenesis its elements proved present TME various human malignancies. renal cell carcinoma (RCC) has recently explored. Clear papillary RCC upregulate most genes relative normal tissue. aim narrative review provide novel insights into disorders.

Язык: Английский

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The role of the complement system in the response to cytotoxic therapy

Seminars in Immunology, Год журнала: 2025, Номер 77, С. 101927 - 101927

Опубликована: Янв. 6, 2025

The complement system is increasingly recognised as a key player in tumour progression and response to cancer treatment. Cytotoxic therapies, including chemo- radiotherapy are standard-of-care for the majority of patients. Cytotoxics have been found alter expression proteins activation components. Many recent reports highlight role local dysregulation microenvironment how targeting such can either anti- or pro-tumoricidal effects depending on several factors treatment scheduling, type its characteristics. This review will explore complex cytotoxic therapy regulation what lessons be learnt identify most effective way therapeutically modulate therapy.

Язык: Английский

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Complement regulators as novel targets for anti-cancer therapy: A comprehensive review

Seminars in Immunology, Год журнала: 2025, Номер 77, С. 101931 - 101931

Опубликована: Янв. 18, 2025

Язык: Английский

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Proteomic profiles of peritoneal fluid-derived small extracellular vesicles correlate with patient outcome in ovarian cancer

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(10)

Опубликована: Апрель 2, 2024

Cancer-derived small extracellular vesicles (sEVs) are capable of modifying tumor microenvironment and promoting progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, secretion such into peritoneal fluid could be determinant factor in dissemination behavior this disease. We designed prospective observational study to assess impact fluid-derived sEVs (PFD-sEVs) OvCa clinical outcome. For purpose, two patient cohorts were enrolled, including cases who underwent diagnostic or cytoreductive surgery, non-oncological patients as controls, surgery for benign gynecological conditions. PFD-sEVs systematic extraction from surgical samples enabled us observe significant quantitative qualitative differences associated with diagnosis, disease stage platinum chemosensitivity. Proteomic profiling led identification molecular pathways proteins interest biological validation S100A4 STX5. In addition, unsupervised analysis proteomic profiles high-grade serous ovarian carcinomas (HGSOC) revealed clusters different outcomes terms overall survival. conclusion, comprehensive characterization content provided prognostic value potential implications HGSOC management.

Язык: Английский

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The role of complement in tumor immune tolerance and drug resistance: a double-edged sword

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 31, 2025

The domain of cancer treatment has persistently been confronted with significant challenges, including those associated recurrence and drug resistance. complement system, which serves as the foundation innate immune exhibits intricate nuanced dual characteristics in evolution tumors. On one hand, system capacity to directly inhibit cell proliferation via specific pathways, thereby exerting a beneficial anti-tumor effect. Conversely, can also facilitate establishment an escape barrier for cells through non-complement-mediated mechanisms, protecting them from eradication. Concurrently, be implicated emergence resistance multitude complex or indirectly reducing efficacy therapeutic interventions facilitating progression cancer. This paper analyses role tumors reviews recent research advances mechanisms tumor tolerance

Язык: Английский

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With complements: C3 inhibition in the clinic

Immunological Reviews, Год журнала: 2022, Номер 313(1), С. 358 - 375

Опубликована: Сен. 25, 2022

Summary C3 is a key complement protein, located at the nexus of all activation pathways. Extracellular, tissue, cell‐derived, and intracellular plays critical roles in immune response that dysregulated many diseases, making it an attractive therapeutic target. However, challenges such as very high concentration blood, increased acute expression, elevated risk infections have historically posed significant development C3‐targeted therapeutics. This further complicated because fragments their receptors trigger complex network downstream effects; therefore, clear understanding these needed to provide context for better mechanism action (MoA) inhibitors, pegcetacoplan. Because C3's differential upstream position C5 cascade, there are mechanistic differences between pegcetacoplan eculizumab determine efficacy patients with paroxysmal nocturnal hemoglobinuria. In this review, we compare MoA hemoglobinuria discuss complement‐mediated disease might be amenable inhibition. We current state outlook therapeutics our perspective on which diseases next success stories journey.

Язык: Английский

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Dissection of paracrine/autocrine interplay in lung tumor microenvironment mimicking cancer cell-monocyte co-culture models reveals proteins that promote inflammation and metastasis

BMC Cancer, Год журнала: 2023, Номер 23(1)

Опубликована: Окт. 2, 2023

Abstract Background Tumor cell-monocyte interactions play crucial roles in shaping up the pro-tumorigenic phenotype and functional output of tumor-associated macrophages. Within tumor microenvironment, such heterotypic cell–cell are known to occur via secretory proteins. Secretory proteins establish a diabolic liaison between cells monocytes, leading their recruitment, subsequent polarization consequent progression. Methods We co-cultured model lung adenocarcinoma cell line A549 with THP-1 delineate them. The levels prototypical pro-inflammatory cytokines like TNF-𝛼, IL-6 anti-inflammatory IL-10 were measured by ELISA. Migration, invasion attachment independence cancer was assessed wound healing, transwell colony formation assays respectively. status EMT evaluated immunofluorescence. Identification differentially expressed monocultures co-culture carried out using SILAC LC–MS/MS. Various insilico tools Cytoscape, Reacfoam, CHAT Kaplan–Meier plotter utilized for association studies, pathway analysis, classification, hallmark relevance predicting prognostic potential candidate Results Co-culture 1:10 ratio showed early release TNF-𝛼 IL-6, however cytokine, observed be released at highest time point. conditioned medium obtained from this promoted migration, as well cells. Co-culturing modulated secretion involved proliferation, invasion, EMT, inflammation, angiogenesis inhibition apoptosis. Among these Versican, Tetranectin, IGFBP2, TUBB4B, C2 IFI30 found correlate inflammatory pro-metastatic milieu our experimental setup. Furthermore, dysregulated expression associated poor prognosis negative disease outcomes compared other types. Pharmacological interventions targeting may serve useful therapeutic approaches adenocarcinoma. Conclusion In study, we have demonstrated that cross-talk modulates IFI30, RNH1, CLEC3B, VCAN, TUBB4B favoring growth metastasis.

Язык: Английский

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The role of the complosome in health and disease

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 10, 2023

The complement system is one of the immune system’s oldest defense mechanisms and historically regarded as a liver-derived serum-active innate that ‘complements’ cell-mediated antibody-mediated responses against pathogens. However, now recognized central component both adaptive immunity at systemic local tissue levels. More findings have uncovered novel activities an intracellularly active system—the complosome—that shifted established functional paradigms in field. complosome has been shown to play critical function regulating T cell responses, physiology (such metabolism), inflammatory disease processes, cancer, which amply proved its immense research potential informed us there still much learn about this system. Here, we summarize current understanding discuss emerging roles health disease.

Язык: Английский

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Limitations and potential of immunotherapy in ovarian cancer

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 9, 2024

Ovarian cancer (OC) is the third most common gynecological and alone has an emergence rate of approximately 308,069 cases worldwide (2020) with dire survival rates. To put it into perspective, mortality OC three times higher than that breast predicted to only increase significantly by 2040. The primary reasons for such a high are physical symptoms detectable during advanced phase disease when resistance chemotherapies around 80% patients do indeed respond chemotherapy initially, show poor prognosis subsequently. This highlights pressing need develop new effective therapies tackle improve patient survival. A major advance in this direction combination immunotherapeutic methods boost CD8

Язык: Английский

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